Toggle Main Menu Toggle Search

Open Access padlockePrints

Endoglin promotes endothelial cell proliferation and TGF-β/ALK1 signal transduction

Lookup NU author(s): Dr Leon Jonker, Professor Helen ArthurORCiD


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Endoglin is a transmembrane accessory receptor for transforming growth factor-β (TGF-β) that is predominantly expressed on proliferating endothelial cells in culture and on angiogenic blood vessels in vivo. Endoglin, as well as other TGF-β signalling components, is essential during angiogenesis. Mutations in endoglin and activin receptor-like kinase 1 (ALK1), an endothelial specific TGF-β type 1 receptor, have been linked to the vascular disorder, hereditary haemorrhagic telangiectasia. However, the function of endoglin in TGF-β/ALK signalling has remained unclear. Here we report that endoglin is required for efficient TGF-β/ALK1 signalling, which indirectly inhibits TGF-β/ALK5 signalling. Endothelial cells lacking endoglin do not grow because TGF-β/ALK1 signalling is reduced and TGF-β/ALK5 signalling is increased. Surviving cells adapt to this imbalance by downregulating ALK5 expression in order to proliferate. The ability of endoglin to promote ALK1 signalling also explains why ectopic endoglin expression in endothelial cells promotes proliferation and blocks TGF-β-induced growth arrest by indirectly reducing TGF-β/ALK5 signalling. Our results indicate a pivotal role for endoglin in the balance of ALK1 and ALK5 signalling to regulate endothelial cell proliferation.

Publication metadata

Author(s): Lebrin F, Goumans M-J, Jonker L, Carvalho RLC, Valdimarsdottir G, Thorikay M, Mummery C, Arthur HM, Ten Dijke P

Publication type: Article

Publication status: Published

Journal: EMBO Journal

Year: 2004

Volume: 23

Issue: 20

Pages: 4018-4028

ISSN (print): 0261-4189

ISSN (electronic): 1460-2075

Publisher: Nature Publishing Group


DOI: 10.1038/sj.emboj.7600386

PubMed id: 15385967


Altmetrics provided by Altmetric